300830-98-2Relevant academic research and scientific papers
Structure-Activity Study on a Novel Series of Macrocyclic Inhibitors of the Hepatitis C Virus NS3 Protease Leading to the Discovery of BILN 2061
Llinàs-Brunet, Montse,Bailey, Murray D.,Bolger, Gordon,Brochu, Christian,Faucher, Anne-Marie,Ferland, Jean Marie,Garneau, Michel,Ghiro, Elise,Gorys, Vida,Grand-Ma?tre, Chantal,Halmos, Ted,Lapeyre-Paquette, Nicole,Liard, Francine,Poirier, Martin,Rhéaume, Manon,Tsantrizos, Youla S.,Lamarre, Daniel
, p. 1605 - 1608 (2007/10/03)
From the discovery of competitive hexapeptide inhibitors, potent and selective HCV NS3 protease macrocyclic inhibitors have been identified. Structure-activity relationship studies were performed focusing on optimizing the N-terminal carbamate and the aromatic substituent on the (4R) -hydroxyproline moiety. Inhibitors meeting the potency criteria in the cell-based assay and with improved oral bioavailability in rats were identified. BILN 2061 was selected as the best compound, the first NS3 protease inhibitor reported with antiviral activity in man.
